DOCSLIB.ORG

Is There a Role for Glutaredoxins and Bolas in the Perception of The

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Is There a Role for Glutaredoxins and Bolas in the Perception of The Is There a Role for Glutaredoxins and BOLAs in the Perception of the Cellular Iron Status in Plants? Pascal Rey, Maël Taupin-Broggini, Jérémy Couturier, Florence Vignols, Nicolas Rouhier To cite this version: Pascal Rey, Maël Taupin-Broggini, Jérémy Couturier, Florence Vignols, Nicolas Rouhier. Is There a Role for Glutaredoxins and BOLAs in the Perception of the Cellular Iron Status in Plants?. Frontiers in Plant Science, Frontiers, 2019, 10, pp.712. 10.3389/fpls.2019.00712. hal-02571980v2 HAL Id: hal-02571980 https://hal-cea.archives-ouvertes.fr/hal-02571980v2 Submitted on 4 Jun 2019 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution| 4.0 International License fpls-10-00712 June 1, 2019 Time: 11:15 # 1 PERSPECTIVE published: 04 June 2019 doi: 10.3389/fpls.2019.00712 Is There a Role for Glutaredoxins and BOLAs in the Perception of the Cellular Iron Status in Plants? Pascal Rey1, Maël Taupin-Broggini2, Jérémy Couturier3, Florence Vignols2 and Nicolas Rouhier3* 1 Plant Protective Proteins Team, CEA, CNRS, BIAM, Aix-Marseille University, Saint-Paul-lez-Durance, France, 2 Biochimie et Physiologie Moléculaire des Plantes, CNRS/INRA/Université de Montpellier/SupAgro, Montpellier, France, 3 Université de Lorraine, INRA, IAM, Nancy, France Glutaredoxins (GRXs) have at least three major identified functions. In apoforms, Edited by: they exhibit oxidoreductase activity controlling notably protein glutathionylation/ Thomas J. Buckhout, deglutathionylation. In holoforms, i.e., iron–sulfur (Fe–S) cluster-bridging forms, they Humboldt University of Berlin, act as maturation factors for the biogenesis of Fe–S proteins or as regulators of iron Germany homeostasis contributing directly or indirectly to the sensing of cellular iron status and/or Reviewed by: Qingyu Wu, distribution. The latter functions seem intimately connected with the capacity of specific Institute of Agricultural Resources GRXs to form [2Fe–2S] cluster-bridging homodimeric or heterodimeric complexes with and Regional Planning (CAAS), China Ping Lan, BOLA proteins. In yeast species, both proteins modulate the localization and/or activity Institute of Soil Science (CAS), China of transcription factors regulating genes coding for proteins involved in iron uptake and *Correspondence: intracellular sequestration in response notably to iron deficiency. Whereas vertebrate Nicolas Rouhier GRX and BOLA isoforms may display similar functions, the involved partner proteins are [email protected] different. We perform here a critical evaluation of the results supporting the implication Specialty section: of both protein families in similar signaling pathways in plants and provide ideas and This article was submitted to experimental strategies to delineate further their functions. Plant Nutrition, a section of the journal Keywords: BOLA, glutaredoxins, iron–sulfur center, maturation factor, iron homeostasis Frontiers in Plant Science Received: 05 March 2019 Accepted: 14 May 2019 INTRODUCTION Published: 04 June 2019 Citation: Many cellular reactions and biological processes require metalloproteins, among which those Rey P, Taupin-Broggini M, containing iron (Fe) cofactors such as mononuclear and dinuclear (non-heme) Fe centers, hemes Couturier J, Vignols F and Rouhier N and iron–sulfur (Fe–S) clusters, are particularly crucial. Unlike other metals such as copper or zinc, (2019) Is There a Role there is no universal Fe chaperone described and so far, only poly rC-binding proteins (PCBPs) were for Glutaredoxins and BOLAs in the Perception of the Cellular Iron shown to coordinate Fe entry in the cytosol and serve for the metalation of non-heme Fe enzymes Status in Plants? in mammals (Philpott et al., 2017). In contrast, the synthesis/assembly of hemes and Fe–S clusters Front. Plant Sci. 10:712. requires more complex and universally conserved pathways (Couturier et al., 2013; Barupala et al., doi: 10.3389/fpls.2019.00712 2016). The machineries dedicated to the maturation of Fe–S proteins present in mitochondria Frontiers in Plant Science| www.frontiersin.org 1 June 2019| Volume 10| Article 712 fpls-10-00712 June 1, 2019 Time: 11:15 # 2 Rey et al. Glutaredoxin-BOLA Interactions and chloroplasts, named ISC (iron–sulfur cluster) and SUF in the b1–b2 loop, referred to as [H/C] loop (Figure 1A; (sulfur mobilization), respectively, are also found in bacteria Li et al., 2011, 2012; Roret et al., 2014; Dlouhy et al., 2016; (Lill, 2009). On the other hand, cytosolic and nuclear Fe–S Nasta et al., 2017). proteins are maturated via the eukaryote-specific cytosolic iron– Hereafter, based on the most recent results and known roles sulfur cluster assembly (CIA) machinery, which is, however, in non-photosynthetic organisms, we discuss the putative or dependent on the mitochondrial ISC machinery for sulfur supply confirmed functions of GRX and BOLA, alone or in complex, in (Lill, 2009). Hence, given the high cellular demand for iron, photosynthetic organisms. sophisticated systems exist to control Fe uptake and intracellular distribution due to its potential toxicity. Strikingly, the Fe sensing systems and associated transcription factors generally differ in THE CLASS II GRX AND BOLA COUPLE bacteria, yeast/fungi, mammals, and plants, but might include PROTEINS PRESENT IN BACTERIA OR common actors such as glutaredoxins (GRXs) and BOLAs (Couturier et al., 2015). IN EUKARYOTE ORGANELLES ARE Two GRX classes, I and II, are present in most INVOLVED IN THE SYNTHESIS OF FE–S organisms whereas additional classes are specific to some CLUSTERS species/genus/kingdoms (Alves et al., 2009; Couturier et al., 2009). GRXs of the first class are involved in redox regulation, The first evidence about GRX involvement in the biogenesis of reducing protein disulfides or glutathione-protein mixed Fe–S proteins were obtained from a S. cerevisiae mutant for disulfides. GRXs from class II participate in the regulation the mitochondrial Grx5 (Table 1; Rodríguez-Manzaneque et al., of Fe homeostasis (Mühlenhoff et al., 2010; Haunhorst et al., 2002; Mühlenhoff et al., 2003). Orthologs of this single domain- 2013) and in the maturation of Fe–S proteins owing to containing GRX are found in bacteria, archaea and plant plastids. their capacity to ligate and exchange [2Fe–2S] clusters with The current view is that Grx5 is required for the maturation partner proteins (Table 1; Rodríguez-Manzaneque et al., 2002; of all types of Fe–S clusters in mitochondria, receiving a [2Fe– Bandyopadhyay et al., 2008). They are also referred to as 2S] cluster from ISCU-type scaffold proteins and transferring monothiol GRXs or CGFS GRXs owing to their conserved CGFS it to ISCA-type transfer proteins for subsequent maturation of active site signature. [4Fe–4S] proteins (Figure 1B). Grx5 is also required for the Regarding the BOLA family, an extensive phylogenetic maturation of nucleo-cytosolic Fe–S proteins and the activation analysis allowed delineating four groups, namely BOLA1– of the Aft1 transcription factor, pointing to its key position in BOLA4 (Couturier et al., 2014). BOLA1s are present in S. cerevisiae (see below) (Uzarska et al., 2013). Yeast Bol1 and both bacteria and eukaryotes, BOLA2s and BOLA3s in Bol3, which have the capacity to form heterodimers with Grx5, eukaryotes and BOLA4s in photosynthetic organisms, archaea, were later shown to be required for a specific set of mitochondrial and bacteria. Pioneer works revealed functions for Escherichia [4Fe–4S] proteins, without affecting de novo synthesis of [2Fe– coli BolA in the regulation of cell morphology, possibly as a 2S] proteins (Uzarska et al., 2016). So far, human BOLA3, transcriptional regulator (Aldea et al., 1989), for Saccharomyces but not BOLA1, has been demonstrated as required for the cerevisiae cytosolic Bol2/Fra2 (Fe repressor of activation 2) maturation of specific Fe–S proteins (Table 1; Cameron et al., in the regulation of iron homeostasis (Lesuisse et al., 2005; 2011; Willems et al., 2013). The client proteins are notably Kumánovics et al., 2008), and for mitochondrial BOLAs (human the succinate dehydrogenase/complex II and lipoate synthase. BOLA3 and yeast Bol1, Bol3) in the maturation of Fe–S Moreover, the fact that bol1–bol31 mutants are neither affected clusters (Table 1; Cameron et al., 2011; Melber et al., 2016; in the CIA machinery, nor in Aft1 activation, indicates that Grx5 Uzarska et al., 2016). has physiological roles independent of Bol1 and Bol3 (Uzarska A very close relationship between class II GRXs and et al., 2016). Additional studies suggested that Bol1 indeed BOLAs was initially evident from genome (gene co-occurrence acts early in the ISC pathway in concert with Grx5 (possibly and clustering, existence of fusion proteins) and large-scale only for [4Fe–4S] proteins) whereas Bol3 may preferentially act interactomic analyses in various organisms (reviewed in with NFU1, a late Fe–S cluster transfer protein, to preserve Przybyla-Toscano et al., 2017). Then, the molecular and the [4Fe–4S] center found in some specific mitochondrial
Load more

Recommended publications
  • Nitrate Reductase from a Neurospora Mutant and a Component of Molybdenum-Enzymes (Nitrogenases/Sulfite Oxidase/E
    Proc. Nat. Acad. Sci. USA Vol. 68, No. 12, pp. 3242-3246, December 1971 In Vitro Formation of Assimilatory Reduced Nicotinamide Adenine Dinucleotide Phosphate: Nitrate Reductase from a Neurospora Mutant and a Component of Molybdenum-Enzymes (nitrogenases/sulfite oxidase/E. coli) ALVIN NASON, KUO-YUNG LEE, SU-SHU PAN, PAUL A. KETCHUM*, ANTONIO LAMBERTI, AND JAMES DEVRIES McCollum-Pratt Institute, The Johns Hopkins University, Baltimore, Maryland 21218. Communicated by Earl R. Stadttman, September 16, 19711 ABSTRACT An active Neurospora-like assimilatory denum moiety. The second component could also be NADPH-nitrate reductase (EC 1.6.6.2), which can be formed in vitro by incubation of extracts of nitrate-in- supplied by the individual molybdenum-enzymes bovine duced Neurospora crassa mutant nit-i with extracts of milk and intestinal xanthine oxidases, chicken liver dehydro- (a) certain other nonallelic nitrate reductase mutants, (b) genase, and rabbit liver aldehyde oxidase (8), provided they uninduced wild type, or (c) xanthine oxidizing and liver were subjected to prior acidification, a treatment known to aldehyde-oxidase systems was also formed by combination dissociate some proteins into their subunits (9-11). (How- of the nit-i extract with other acid-treated enzymes known to contain molybdenum. These molybdenum ever, sodium molybdate and some 20 different partially puri- enzymes included (a) nitrogenase, or its molybdenum- fied enzymes that do not contain molybdenum were inactive.) iron protein, from Clostridium, Azotobacter, and
    [Show full text]
  • A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
    Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated.
    [Show full text]
  • Pro-Aging Effects of Xanthine Oxidoreductase Products
    antioxidants Review Pro-Aging Effects of Xanthine Oxidoreductase Products , , Maria Giulia Battelli y , Massimo Bortolotti y , Andrea Bolognesi * z and Letizia Polito * z Department of Experimental, Diagnostic and Specialty Medicine-DIMES, Alma Mater Studiorum, University of Bologna, Via San Giacomo 14, 40126 Bologna, Italy; [email protected] (M.G.B.); [email protected] (M.B.) * Correspondence: [email protected] (A.B.); [email protected] (L.P.); Tel.: +39-051-20-9-4707 (A.B.); +39-051-20-9-4729 (L.P.) These authors contributed equally. y Co-last authors. z Received: 22 July 2020; Accepted: 4 September 2020; Published: 8 September 2020 Abstract: The senescence process is the result of a series of factors that start from the genetic constitution interacting with epigenetic modifications induced by endogenous and environmental causes and that lead to a progressive deterioration at the cellular and functional levels. One of the main causes of aging is oxidative stress deriving from the imbalance between the production of reactive oxygen (ROS) and nitrogen (RNS) species and their scavenging through antioxidants. Xanthine oxidoreductase (XOR) activities produce uric acid, as well as reactive oxygen and nitrogen species, which all may be relevant to such equilibrium. This review analyzes XOR activity through in vitro experiments, animal studies and clinical reports, which highlight the pro-aging effects of XOR products. However, XOR activity contributes to a regular level of ROS and RNS, which appears essential for the proper functioning of many physiological pathways. This discourages the use of therapies with XOR inhibitors, unless symptomatic hyperuricemia is present.
    [Show full text]
  • Lung Proteomic Biomarkers Associated with Chronic Obstructive Pulmonary Disease
    medRxiv preprint doi: https://doi.org/10.1101/2021.04.07.21255030; this version posted April 10, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Lung proteomic biomarkers associated with chronic obstructive pulmonary disease Yu-Hang Zhang1, Michael R. Hoopmann2, Peter J. Castaldi1, Kirsten A. Simonsen2, Mukul K. Midha2, Michael H. Cho1, Gerard J. Criner3, Raphael Bueno4, Jiangyuan Liu1, Robert L. Moritz2*, Edwin K. Silverman1* 1Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA 2Institute for Systems Biology, Seattle, WA, USA 3Temple University School of Medicine, Philadelphia, PA, USA 4Division of Thoracic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA * These senior authors contributed equally to this work Corresponding Authors: Edwin K. Silverman, Email: [email protected] Robert L. Moritz, Email: [email protected] Keywords: chronic obstructive pulmonary disease, proteomics, biomarkers, mass spectrometry, machine learning NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2021.04.07.21255030; this version posted April 10, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. ABSTRACT Background: Identifying protein biomarkers for chronic obstructive pulmonary disease (COPD) has been challenging.
    [Show full text]
  • The Link Between Purine Metabolism and Production of Antibiotics in Streptomyces
    antibiotics Review The Link between Purine Metabolism and Production of Antibiotics in Streptomyces Smitha Sivapragasam and Anne Grove * Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA; [email protected] * Correspondence: [email protected] Received: 10 May 2019; Accepted: 3 June 2019; Published: 6 June 2019 Abstract: Stress and starvation causes bacterial cells to activate the stringent response. This results in down-regulation of energy-requiring processes related to growth, as well as an upregulation of genes associated with survival and stress responses. Guanosine tetra- and pentaphosphates (collectively referred to as (p)ppGpp) are critical for this process. In Gram-positive bacteria, a main function of (p)ppGpp is to limit cellular levels of GTP, one consequence of which is reduced transcription of genes that require GTP as the initiating nucleotide, such as rRNA genes. In Streptomycetes, the stringent response is also linked to complex morphological differentiation and to production of secondary metabolites, including antibiotics. These processes are also influenced by the second messenger c-di-GMP. Since GTP is a substrate for both (p)ppGpp and c-di-GMP, a finely tuned regulation of cellular GTP levels is required to ensure adequate synthesis of these guanosine derivatives. Here, we discuss mechanisms that operate to control guanosine metabolism and how they impinge on the production of antibiotics in Streptomyces species. Keywords: c-di-GMP; guanosine and (p)ppGpp; purine salvage; secondary metabolism; Streptomycetes; stringent response 1. Introduction Bacteria experience constant challenges, either in the environment or when infecting a host. They utilize various mechanisms to survive such stresses, which may include changes in temperature, pH, or oxygen content as well as limited access to carbon or nitrogen sources.
    [Show full text]
  • Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
    Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase
    [Show full text]
  • Role of GSH and Iron-Sulfur Glutaredoxins in Iron Metabolism—Review
    molecules Review Role of GSH and Iron-Sulfur Glutaredoxins in Iron Metabolism—Review 1, 1, 1 1 Trnka Daniel y , Hossain Md Faruq y , Jordt Laura Magdalena , Gellert Manuela and Lillig Christopher Horst 2,* 1 Institute for Medical Biochemistry and Molecular Biology, University Medicine, University of Greifswald, 17475 Greifswald, Germany; [email protected] (T.D.); [email protected] (H.M.F.); [email protected] (J.L.M.); [email protected] (G.M.) 2 Christopher Horst Lillig, Institute for Medical Biochemistry and Molecular Biology, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475 Greifswald, Germany * Correspondence: [email protected]; Tel.: +49-3834-865407; Fax: +49-3834-865402 These authors contributed equally to this work. y Academic Editor: Pál Perjési Received: 29 July 2020; Accepted: 22 August 2020; Published: 25 August 2020 Abstract: Glutathione (GSH) was initially identified and characterized for its redox properties and later for its contributions to detoxification reactions. Over the past decade, however, the essential contributions of glutathione to cellular iron metabolism have come more and more into focus. GSH is indispensable in mitochondrial iron-sulfur (FeS) cluster biosynthesis, primarily by co-ligating FeS clusters as a cofactor of the CGFS-type (class II) glutaredoxins (Grxs). GSH is required for the export of the yet to be defined FeS precursor from the mitochondria to the cytosol. In the cytosol, it is an essential cofactor, again of the multi-domain CGFS-type Grxs, master players in cellular iron and FeS trafficking. In this review, we summarize the recent advances and progress in this field. The most urgent open questions are discussed, such as the role of GSH in the export of FeS precursors from mitochondria, the physiological roles of the CGFS-type Grx interactions with BolA-like proteins and the cluster transfer between Grxs and recipient proteins.
    [Show full text]
  • Proteomic Profiling of Glucocorticoid-Exposed Myogenic
    Proteome Science BioMed Central Research Open Access Proteomic profiling of glucocorticoid-exposed myogenic cells: Time series assessment of protein translocation and transcription of inactive mRNAs Erica KM Reeves, Heather Gordish-Dressman, Eric P Hoffman* and Yetrib Hathout Address: Research Center for Genetic Medicine, Children's National Medical Center, 111 Michigan Ave NW, Washington DC. 20010, USA Email: Erica KM Reeves - [email protected]; Heather Gordish-Dressman - [email protected]; Eric P Hoffman* - [email protected]; Yetrib Hathout - [email protected] * Corresponding author Published: 30 July 2009 Received: 10 March 2009 Accepted: 30 July 2009 Proteome Science 2009, 7:26 doi:10.1186/1477-5956-7-26 This article is available from: http://www.proteomesci.com/content/7/1/26 © 2009 Reeves et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Prednisone, one of the most highly prescribed drugs, has well characterized effects on gene transcription mediated by the glucocorticoid receptor. These effects are typically occurring on the scale of hours. Prednisone also has a number of non-transcriptional effects (occurring on minutes scale) on protein signaling, yet these are less well studied. We sought to expand the understanding of acute effects of prednisone action on cell signaling using a combination of SILAC strategy and subcellular fractionations from C2C12 myotubes. Results: De novo translation of proteins was inhibited in both SILAC labeled and unlabeled C2C12 myotubes.
    [Show full text]
  • Monitoring the Redox Status in Multiple Sclerosis
    Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 31 July 2020 doi:10.20944/preprints202007.0737.v1 Review Monitoring the Redox Status in Multiple Sclerosis Masaru Tanaka 1,2 and László Vécsei 1,2,* 1 MTA-SZTE, Neuroscience Research Group, Semmelweis u. 6, Szeged, H-6725 Hungary; [email protected] 2 Department of Neurology, Interdisciplinary Excellence Centre, Faculty of Medicine, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary * Correspondence: [email protected]; Tel.: +36-62-545-351 Received: date; Accepted: date; Published: date Abstract: Worldwide, over 2.2 million people are suffered from multiple sclerosis (MS), a multifactorial demyelinating disease of the central nervous system, characterized by multifocal inflammatory or demyelinating attacks associated with neuroinflammation and neurodegeneration. The blood, cerebrospinal fluid, and postmortem brain samples of MS patients evidenced the presence of reduction-oxidation (redox) homeostasis disturbance such as the alternations of oxidative and antioxidative enzyme activities and the presence of degradation products. This review article discussed the components of redox homeostasis including reactive chemical species, oxidative enzymes, antioxidative enzymes, and degradation products. The reactive chemical species covered frequently discussed reactive oxygen/nitrogen species, rarely featured reactive chemicals such as sulfur, carbonyls, halogens, selenium, and nucleophilic species that potentially act as reductive as well as pro-oxidative stressors. The antioxidative enzyme systems covered the nuclear factor erythroid-2-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 (KEAP1) signaling pathway, a possible biomarker sensitive to the initial phase of oxidative stress. Altered components of the redox homeostasis in MS were discussed, some of which turned to be MS subtype- or treatment-specific and thus potentially become diagnostic, prognostic, predictive, and/or therapeutic biomarkers.
    [Show full text]
  • Xanthine Oxidase Mediates Hypoxia-Inducible Factor-2A Degradation by Intermittent Hypoxia
    Xanthine Oxidase Mediates Hypoxia-Inducible Factor-2a Degradation by Intermittent Hypoxia Jayasri Nanduri*, Damodara Reddy Vaddi, Shakil A. Khan, Ning Wang, Vladislav Makerenko, Nanduri R. Prabhakar Institute for Integrative Physiology and Center for Systems Biology of O2 Sensing, Biological Sciences Division, University of Chicago, Chicago, Illinois, United States of America Abstract Sleep-disordered breathing with recurrent apnea produces chronic intermittent hypoxia (IH). We previously reported that IH leads to down-regulation of HIF-2a protein via a calpain-dependent signaling pathway resulting in oxidative stress. In the present study, we delineated the signaling pathways associated with calpain-dependent HIF-2a degradation in cell cultures and rats subjected to chronic IH. Reactive oxygen species (ROS) scavengers prevented HIF-2a degradation by IH and ROS mimetic decreased HIF-2a protein levels in rat pheochromocytoma PC12 cell cultures, suggesting that ROS mediate IH- induced HIF-2a degradation. IH activated xanthine oxidase (XO) by increased proteolytic conversion of xanthine dehydrogenase to XO. ROS generated by XO activated calpains, which contributed to HIF-2a degradation by IH. Calpain- induced HIF-2a degradation involves C-terminus but not the N-terminus of the HIF-2a protein. Pharmacological blockade as well as genetic knock down of XO prevented IH induced calpain activation and HIF-2a degradation in PC12 cells. Systemic administration of allopurinol to rats prevented IH-induced hypertension, oxidative stress and XO activation in adrenal medulla. These results demonstrate that ROS generated by XO activation mediates IH-induced HIF-2a degradation via activation of calpains. Citation: Nanduri J, Vaddi DR, Khan SA, Wang N, Makerenko V, et al.
    [Show full text]
  • Free Radical in Ischemia/Reperfusion Injury
    77:222 Spring 2003 Free Radicals in Biology and Medicine Page 0 This student paper was written as an assignment in the graduate course Free Radicals in Biology and Medicine (77:222, Spring 2003) offered by the Free Radical and Radiation Biology Program B-180 Med Labs The University of Iowa Iowa City, IA 52242-1181 Spring 2003 Term Instructors: GARRY R. BUETTNER, Ph.D. LARRY W. OBERLEY, Ph.D. with guest lectures from: Drs. Freya Q . Schafer, Douglas R. Spitz, and Frederick E. Domann The Fine Print: Because this is a paper written by a beginning student as an assignment, there are no guarantees that everything is absolutely correct and accurate. In view of the possibility of human error or changes in our knowledge due to continued research, neither the author nor The University of Iowa nor any other party who has been involved in the preparation or publication of this work warrants that the information contained herein is in every respect accurate or complete, and they are not responsible for any errors or omissions or for the results obtained from the use of such information. Readers are encouraged to confirm the information contained herein with other sources. All material contained in this paper is copyright of the author, or the owner of the source that the material was taken from. This work is not intended as a threat to the ownership of said copyrights. Gang Niu Ischemia/reperfusion Injury 1 of 20 Free Radical in Ischemia/reperfusion Injury By Gang Niu Free Radical and Radiation Biology Program B-180 Medical Laboratories The University of Iowa Iowa City, IA 52242-1181, USA For 077:222 Spring 2003 08, May 2003 Paper V Abbreviations IR Ischemia reperfusion PUFA Polyunsaturated fatty acid ROS Reactive oxygen species SOD Superoxide dismutase XDH Xanthine dehydrogenase XO Xanthine oxidase Gang Niu Ischemia/reperfusion Injury 2 of 20 Table of Contents Abstract..........................................................................................................................................
    [Show full text]
  • Structural and Biochemical Insights Into the Multiple Functions of Yeast Grx3
    Article Structural and Biochemical Insights into the Multiple Functions of Yeast Grx3 Chang-Biao Chi, YaJun Tang, Jiahai Zhang, Ya-Nan Dai, Mohnad Abdalla, Yuxing Chen and Cong-Zhao Zhou School of Life Sciences and Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of China Key Laboratory of Structural Biology, Chinese Academy of Science, Hefei, Anhui, 230027, People's Republic of China Correspondence to YaJun Tang and Cong-Zhao Zhou: School of Life Sciences and Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of China. [email protected]; [email protected] https://doi.org/10.1016/j.jmb.2018.02.024 Edited by Charalampo Kalodimos Abstract The yeast Saccharomyces cerevisiae monothiol glutaredoxin Grx3 plays a key role in cellular defense against oxidative stress and more importantly, cooperates with BolA-like iron repressor of activation protein Fra2 to regulate the localization of the iron-sensing transcription factor Aft2. The interplay among Grx3, Fra2 and Aft2 responsible for the regulation of iron homeostasis has not been clearly described. Here we solved the crystal structures of the Trx domain (Grx3Trx) and Grx domain (Grx3Grx) of Grx3 in addition to the solution structure of Fra2. Structural analyses and activity assays indicated that the Trx domain also contributes to the glutathione S-transferase activity of Grx3, via an inter-domain disulfide bond between Cys37 and Cys176. NMR titration and pull-down assays combined with surface plasmon resonance experiments revealed that Fra2 could form a noncovalent heterodimer with Grx3 via an interface between the helix-turn-helix motif of Fra2 and the C- terminal segment of Grx3Grx, different from the previously identified covalent heterodimer mediated by Fe–S cluster.
    [Show full text]